Natural History of Morquio B and Late-Onset of GM1 Gangliosidosis

study id #: NCT04320329

condition: Morquio B Disease, GM1 Gangliosidosis Type III

status: Not yet recruiting

Mucopolysaccharidosis type IVB (Morquio-B disease, MBD) is an autosomal-recessive lysosomal disease caused by mutations in a gene called GLB1. Clinically, Morquio B presents with progressive skeletal deformities involving mostly long bones and spine. While the information on GLB1 mutations associated with MBD is limited, there is a significant overlap in clinical presentation between Morquio B and late-onset GM1 gangliosidosis with both conditions being caused by mutations in the same GLB1 gene. In this study, the investigators plan to collect retrospective data from patients’ medical charts, as well as, information from the prospective follow up clinic visits. There will be two study visits with the interval of one year. The study procedures will include a detailed physical exam, bone scans, heart and lung function, physical endurance tests, hearing test, laboratory tests and quality of life surveys.

The purpose of this study is to collect data on the natural history of Morquio B and to create a biobank of laboratory samples (blood, urine and skin cells) for future research. This information will improve the understanding of the natural progression of Morquio B disease.

results: https://clinicaltrials.gov/ct2/show/results/NCT04320329

last updated: February 26, 2022

start date: June 1, 2020

estimated completion: May 31, 2022

last updated: April 30, 2020

size / enrollment: 30

study description: The primary objective of this study is to establish the natural history of Morquio B (Mucopolysaccharidosis type IVB, MBD) disease through the collection and analysis of retrospective and prospective data on patients diagnosed with Morquio B. Because of significant overlap in clinical presentation, patients with late-onset GM1 will also be included.

Upon consent, data from clinical, laboratory, functional and quality of life studies, and data from review of medical records will be collected and analyzed descriptively. In addition, the samples of blood, urine and fibroblasts will be collected and stored at BC Children Hospital Research Institute Biobank for future research. The prospective follow up will include two clinic visits, one year apart. The following data will be collected during the prospective observational part of the study (as per study protocol) and retrospective part (whether such data are available from the medical chart):

Medical history: Morquio B / Late-onset GM1 gangliosidosis diagnosis, presentation, treatments and symptom progression
Physical exam, including neurological and ophthalmological assessments
Standard Grip Strength Evaluation
Range of motion
Six-minute walk test (6MWT)
3-Minute Stair Climb Test
Gait and Motion assessment
Pulmonary function testing
Hearing test
Echocardiography
EKG
X-ray (lumbar spine, upper & lower limbs, hip)
DXA scan
Brain MRI
Laboratory tests (GAGs assay and pro-inflammatory cytokine panel)
Blood, urine and fibroblast samples for biobanking
Genetic test (if not done per standard of care)

Additional assessments and evaluations:

• Patient-reported outcomes: quality of life SF-36, MPS HAQ and the interview on personally meaningful outcomes

primary outcomes:

• Physical Development
  Height
• Through study completion, an average of 1 year
  Physical Development
  Weight
• Through study completion, an average of 1 year
  Physical Development
  Growth rate
• Through study completion, an average of 1 year
  Physical Endurance
  6MWT
• 1 year
  Physical Endurance
  3MSCT
• 1 year
  Physical Endurance
  Standard Grip Strength evaluation
• 1 year
  Range of Motion Scale
  Assessments: shoulder, elbow, wrist, hip, knee, ankle
• Through study completion, an average of 1 year
  Skeletal involvement
  X-ray studies, pQCT (where available), DXA of lateral distal femur, x-ray and/or MRI of cervical spine to assess spinal stenosis and spinal cord compression; X-ray of cervical spine to assess odontoid hypoplasia and atlantoaxial instability
• Through study completion, an average of 1 year
  CNS involvement
  Neurological assessments, Brain MRI
• Through study completion, an average of 1 year
  Surrogate biomarkers
  Glycosaminoglycans (GAGs): keratan sulfate, heparan sulfate, dermatan sulfate, chondroitin-6-sulfate
• Baseline and 1 year
  Surrogate biomarkers
  Comprehensive pro-inflammatory cytokine panel with markers of bone turnover
• Baseline and 1 year
  Health-related Quality of Life (HRQoL)
  SF-36
• Baseline and 1 year
  Health-related Quality of Life (HRQoL) and Activities of Daily living (ADLs)
  MPS-HAQ
• Baseline and 1 year
  Personally Meaningful Outcomes
  PMO Questionnaire
• Baseline and 1 year
  

inclusion criteria:

exclusion criteria: Criteria:

Previous Hematopoietic Stem Cell Transplant procedure (HSCT);
Concurrent disease or condition that would interfere with participation in the study and/or travel to the site (for the prospective follow up);
Previous or current casual treatments that might affect the natural course of the disease;
Patient's (guardian's) not understanding and/or not agreeing to the informed consent form;
GM1-gangliosidosis patients who present without "MPSIVB skeletal phenotype"

sponsor: University of British Columbia

contacts: Nataliya Yuskiv, Dr, 6048752000, [email protected]

trial center locations: Canada

• Canada, British Columbia
  BC Children’s Hospital